Optimization of Y-90 Radioembolization Imaging for Post-Treatment Dosimetry on a Long Axial Field-of-View PET/CT Scanner.

BACKGROUND: PET imaging after yttrium-90 (Y-90) radioembolization is challenging because of the low positron fraction of Y-90 (32 × 10-6). The resulting low number of events can be compensated by the high sensitivity of long axial field-of-view (LAFOV) PET/CT scanners. Nevertheless, the reduced event statistics require optimization of the imaging protocol to achieve high image quality (IQ) and quantification accuracy sufficient for post-treatment dosimetry. METHODS: Two phantoms (NEMA IEC and AbdoMan phantoms, mimicking human liver) filled with Y-90 and a 4:1 sphere (tumor)-to-background ratio were scanned for 24 h with the Biograph Vision Quadra (Siemens Healthineers). Eight patients were scanned after Y-90 radioembolization (1.3-4.7 GBq) using the optimized protocol (obtained by phantom studies). The IQ, contrast recovery coefficients (CRCs) and noise were evaluated for their limited and full acceptance angles, different rebinned scan durations, numbers of iterations and post-reconstruction filters. The s-value-based absorbed doses were calculated to assess their suitability for dosimetry. RESULTS: The phantom studies demonstrate that two iterations, five subsets and a 4 mm Gaussian filter provide a reasonable compromise between a high CRC and low noise. For a 20 min scan duration, an adequate CRC of 56% (vs. 24 h: 62%, 20 mm sphere) was obtained, and the noise was reduced by a factor of 1.4, from 40% to 29%, using the full acceptance angle. The patient scan results were consistent with those from the phantom studies, and the impacts on the absorbed doses were negligible for all of the studied parameter sets, as the maximum percentage difference was -3.89%. CONCLUSIONS: With 2i5s, a 4 mm filter and a scan duration of 20 min, IQ and quantification accuracy that are suitable for post-treatment dosimetry of Y-90 radioembolization can be achieved.

Dual-Time-Point Posttherapy 177Lu-PSMA-617 SPECT/CT Describes the Uptake Kinetics of mCRPC Lesions and Prognosticates Patients' Outcome.

177Lu-PSMA-617 is an effective therapeutic option in metastasized castration-resistant prostate cancer (mCRPC). However, some patients progress under treatment. We hypothesized that the tracer kinetics within the metastases may influence the therapy effectiveness and tested this hypothesis by analyzing uptake parameters on 2 consecutive posttherapy SPECT/CT scans. Methods: mCRPC patients treated with 177Lu-PSMA-617 and with available posttherapy SPECT/CT imaging (24 and 48 h after the first treatment) were enrolled retrospectively. Volumes of interest were defined on lymph node metastasis (LNM) and bone metastasis (BM) on both SPECT/CT scans. The reduction of the percentage injected dose (%IDred) between the 2 SPECT/CT scans was computed. We compared %IDred of responders (prostate-specific antigen drop ≥ 50% after 2 cycles of 177Lu-PSMA-617) and nonresponders. We tested the association of %IDred with progression-free survival and overall survival (OS) using a univariate Kaplan-Meier (KM) analysis and a multivariate Cox regression model. Results: Fifty-five patients (median age, 73 y; range, 54-87 y) were included. %IDred in LNM and BM was greater in nonresponders than in responders (for LNM, 36% in nonresponders [interquartile range (IQR), 26%-47%] vs. 24% in responders [IQR, 12%-33%] [P = 0.003]; for BM, 35% in nonresponders [IQR, 27%-52%] vs. 18% in responders [IQR, 15%-29%] [P = 0.002]). For progression-free survival, in KM analysis, greater %IDred in LNM (P = 0.008) and BM (P = 0.001) was associated with shorter survival, whereas in multivariate analysis, only %IDred in LNM was retained (P = 0.03). In univariate KM analysis of OS, greater %IDred in BM was associated with shorter survival (P = 0.002). In multivariate OS analysis, BM %IDred (P = 0.009) was retained. Conclusion: The 177Lu-PSMA-617 clearance rate from mCRPC metastases appears to be a relevant prognosticator of response and survival, with faster clearing possibly signaling a shorter radiopharmaceutical residence time and absorbed dose. Dual-time-point analysis appears to be a feasible and readily available approach to estimate the likelihood of response and patients' survival.

Image quality assessment along the one metre axial field-of-view of the total-body Biograph Vision Quadra PET/CT system for 18F-FDG.

AIM: Recently, total-body PET/CT systems with an extended axial field-of-view (aFOV) became commercially available which allow acquiring physiologic information of multiple organs simultaneously. However, the nominal aFOV may clinically not be used effectively due to the inherently reduced sensitivity at the distal ends of the aFOV. The aim of this study was to assess the extent of the useful aFOV of the Biograph Vision Quadra PET/CT system. METHODS: A NEMA image quality (IQ) phantom mimicking a standard [18F]FDG examination was used. Image contrast and noise were assessed across the 106 cm aFOV of the Biograph Vision Quadra PET/CT system (Siemens Healthineers). Phantom acquisitions were performed at different axial positions. PET data were rebinned to simulate different acquisition times for a standard injected activity and reconstructed using different filter settings to evaluate the noise and images along the axial direction. RESULTS: Image noise and contrast were stable within the central 80 cm of the aFOV. Outside this central area, image contrast variability as well as image noise increased. This degradation of IQ was in particular evident for short acquisition times of less than 30 s. At 10 min acquisition time and in the absence of post-reconstruction filtering, the useful aFOV was 100 cm. For a 2 min acquisition time, a useful aFOV with image noise below 15% was only achievable using Gaussian filtering with axial extents of between 83 and 103 cm when going from 2 to 6 mm full-width-half-maximum, respectively. CONCLUSION: Image noise increases substantially towards the ends of the aFOV. However, good IQ in compliance with generally accepted benchmarks is achievable for an aFOV of > 90 cm. When accepting higher image noise or using dedicated protocol settings such as stronger filtering a useful aFOV of around 1 m can be achieved for a 2 min acquisition time.

Correlation of C-arm CT acquired parenchymal blood volume (PBV) with 99mTc-macroaggregated albumin (MAA) SPECT/CT for radioembolization work-up.

OBJECTIVE: SPECT/CT with 99mTc-macroaggregated albumin (MAA) is generally used for diagnostic work-up prior to transarterial radioembolization (TARE) to exclude shunts and to provide additional information for treatment stratification and dose calculation. C-arm CT is used for determination of lobular vascular supply and assessment of parenchymal blood volume (PBV). Aim of this study was to correlate MAA-uptake and PBV-maps in hepatocellular carcinoma (HCC) and hepatic metastases of the colorectal carcinoma (CRC). MATERIALS AND METHODS: 34 patients underwent a PBV C-arm CT immediately followed by 99mTc-MAA injection and a SPECT/CT acquisition after 1 h uptake. MAA-uptake and PBV-maps were visually assessed and semi-quantitatively analyzed (MAA-tumor/liver-parenchyma = MAA-TBR or PBV in ml/100ml). In case of a poor match, tumors were additionally correlated with post-TARE 90Y-Bremsstrahlung-SPECT/CT as a reference. RESULTS: 102 HCC or CRC metastases were analyzed. HCC presented with significantly higher MAA-TBR (7.6 vs. 3.9, p<0.05) compared to CRC. Tumors showed strong intra- and inter-individual dissimilarities between TBR and PBV with a weak correlations for capsular HCCs (r = 0.45, p<0.05) and no correlation for CRC. The demarcation of lesions was slightly better for both HCC and CRC in PBV-maps compared to MAA-SPECT/CT (exact match: 52%/50%; same intensity/homogeneity: 38%/39%; insufficient 10%/11%). MAA-SPECT/CT revealed a better visual correlation with post-therapeutic 90Y-Bremsstrahlung-SPECT/CT. CONCLUSION: The acquisition of PBV can improve the detectability of small intrahepatic tumors and correlates with the MAA-Uptake in HCC. The results indicate that 99mTc-MAA-SPECT/CT remains to be the superior method for the prediction of post-therapeutic 90Y-particle distribution, especially in CRC. However, intra-procedural PBV acquisition has the potential to become an additional factor for TARE planning, in addition to improving the determination of segment and tumor blood supply, which has been demonstrated previously.

Transitioning to whole-body SPECT/CT in prostate cancer staging: a new concept for a better imaging workflow.

AIM: Whole-body bone scan (BS) is the clinical standard in detecting bone metastases in prostate cancer patients. Additional SPECT/CT has allowed to significantly increase its diagnostic accuracy. However, performing both planar and additional SPECT/CT prolongs the total examination time and lowers patient throughput. In this study we aim to assess the diagnostic performance of a SPECT/CT-only protocol compared to the traditional procedure that is BS with a facultative SPECT/CT in case of unclear findings. METHODS: 50 patients with high-risk prostate cancer and suspected bone metastases were enrolled in this retrospective study. All patients received a whole-body Tc-99m-DPD BS followed by a 3 field-of-view (FOV) SPECT/CT (GE Discovery 670 Pro®) covering an area from the vertex to the mid-femur. Metastatic lesions were evaluated visually on BS and SPECT/CT and correlated to PSA-levels. RESULTS: Detection rate was up to 50 % higher in SPECT/CT than in BS (n = 2829 vs. n = 1942; p < 0.001), but 31/1942 (1.5 %) lesions detected on BS were located out of the SPECT/CT field-of-view. In our analysis a PSA-level of > 80 µg/l could be defined as a cut-off-value for metastatic spread beyond mid-thigh, as no patient with PSA< 80 µg/l had localizations outside the SPECT/CT field-of-view (AUCPSA = 0.95, p < 0.001 sensitivity: 100 %, specificity: 77 %, NPV: 100 %, PPV: 67 %). The SPECT/CT-only protocol did not prolong acquisition time significantly as compared to BS. CONCLUSIONS: In patients with high-risk prostate cancer presenting with PSA < 80 µg/l and absent clinical symptoms, vertex to mid-thighs 3-FOV-SPECT/CT was representative for the entire skeletal system and was able to detect more lesions than planar acquisition. This procedure did not prolong patient handling time significantly.

Is the standard uptake value (SUV) appropriate for quantification in clinical PET imaging? - Variability induced by different SUV measurements and varying reconstruction methods.

INTRODUCTION: PET quantification using the standard uptake value (SUV) is very prone to variations by technical factors of the scanner system and patient specific characteristics. Aim of the study was to investigate the reproducibility of SUV values between different measures and different reconstruction algorithms in a PET/CT scanner of the newest generation. METHODS: The time-of-flight PET datasets of 27 consecutive oncological patients were reconstructed with OSEM3D in two different matrix sizes (200 × 200 and 400 × 400) as well as in a matrix size of 400 × 400 and additional point-spread-reconstruction. The standardized uptake values SUVmax, SUVmean and SUVpeak in 60 lesions were compared concerning their variability in the three reconstructions. RESULTS: The addition of point-spread-reconstruction causes a significant increase of SUV values in comparison to OSEM 3D. SUVpeak showed the highest reproducibility between the different reconstruction algorithms. The variability of SUVmax and SUVmean increases in small lesions <5 ml, while SUVpeak remains more stable. CONCLUSION: SUVmax, SUVmean and SUVpeak can be used for PET quantification in principle. However, quantification of small lesions is difficult. SUVpeak is the most robust method when using varying reconstruction methods, especially in small lesions.

On the quantification accuracy, homogeneity, and stability of simultaneous positron emission tomography/magnetic resonance imaging systems.

OBJECTIVE: A potential major application of simultaneous avalanche photodiode-based positron emission tomography (PET)/magnetic resonance imaging (MRI) systems are quantitative brain studies for cerebral blood flow measurements in combination with blood-oxygen-level-dependent or perfusion MRI, requiring a high performance for both modalities. Thus, we evaluated PET quantification accuracy and homogeneity for 2 different simultaneous PET/MRI systems (whole-body and brain scanner) compared with those of a state-of-the-art PET detector (PET/computed tomography) using phantom studies. In addition, we investigated the long-term stability of PET and quality of functional MRI measurements of a clinical whole-body PET/MRI scanner. MATERIALS AND METHODS: Phantom measurements were conducted using spheres filled with [F]-fluoride distributed in a homogeneous cylinder phantom at different positions inside the PET field of view. Recovery values and standard deviations were extracted from resulting PET images. The influence of magnetic resonance-based attenuation correction and that of activity outside the PET field of view on the recovery values of these spheres was evaluated. Furthermore, long-term PET stability of the whole-body PET/MRI system was assessed by evaluating position profiles, energy spectra, count rates, and recovery values from [Ge]-phantom scans. Functional MRI applicability was tested in accordance with the functional Biomedical Information Research Network procedure. RESULTS: The BrainPET system showed high recovery values (up to 99%) but also increased variability (up to 7.4%). Significant underestimations in PET quantification near activity outside the PET field of view were found (up to 80%). Using magnetic resonance-based attenuation correction led to an underestimation in PET activity of approximately 7%. In distinction, the whole-body PET/MRI system revealed performance similar to the PET/computed tomographic scanner (recovery values up to approximately 60% with a variability of approximately 4%). Long-term stability and fMRI performance of the whole-body PET/MRI scanner showed no degradation compared with stand-alone systems. CONCLUSIONS: Homogeneity and accuracy of avalanche photodiode-based PET detectors is comparable with those of the state-of-the-art detectors based on photomultiplier tubes. However, attenuation correction on PET/MRI systems has to be adapted carefully for quantitative PET measurements. The BrainPET system needs improved scatter correction to perform quantitative brain studies. The whole-body PET/MRI scanner, however, is applicable for quantitative brain studies.

Effect of MR contrast agents on quantitative accuracy of PET in combined whole-body PET/MR imaging.

PURPOSE: Clinical PET/MR acquisition protocols entail the use of MR contrast agents (MRCA) that could potentially affect PET quantification following MR-based attenuation correction (AC). We assessed the effect of oral and intravenous (IV) MRCA on PET quantification in PET/MR imaging. METHODS: We employed two MRCA: Lumirem (oral) and Gadovist (IV). First, we determined their reference PET attenuation values using a PET transmission scan (ECAT-EXACT HR+, Siemens) and a CT scan (PET/CT Biograph 16 HI-REZ, Siemens). Second, we evaluated the attenuation of PET signals in the presence of MRCA. Phantoms were filled with clinically relevant concentrations of MRCA in a background of water and (18)F-fluoride, and imaged using a PET/CT scanner (Biograph 16 HI-REZ, Siemens) and a PET/MR scanner (Biograph mMR, Siemens). Third, we investigated the effect of clinically relevant volumes of MRCA on MR-based AC using human pilot data: a patient study employing Gadovist (IV) and a volunteer study employing two different oral MRCA (Lumirem and pineapple juice). MR-based attenuation maps were calculated following Dixon-based fat-water segmentation and an external atlas-based and pattern recognition (AT&PR) algorithm. RESULTS: IV and oral MRCA in clinically relevant concentrations were found to have PET attenuation values similar to those of water. The phantom experiments showed that under clinical conditions IV and oral MRCA did not yield additional attenuation of PET emission signals. Patient scans showed that PET attenuation maps are not biased after the administration of IV MRCA but may be biased, however, after ingestion of iron oxide-based oral MRCA when segmentation-based AC algorithms are used. Alternative AC algorithms, such as AT&PR, or alternative oral contrast agents, such as pineapple juice, can yield unbiased attenuation maps. CONCLUSION: In clinical PET/MR scenarios MRCA are not expected to lead to markedly increased attenuation of the PET emission signals. MR-based attenuation maps may be biased by oral iron oxide-based MRCA unless advanced AC algorithms are used.

The effect of patient positioning aids on PET quantification in PET/MR imaging.

OBJECTIVES: Clinical PET/MR requires the use of patient positioning aids to immobilize and support patients for the duration of the combined examination. Ancillary immobilization devices contribute to overall attenuation of the PET signal, but are not detected with conventional MR sequences and, hence, are ignored in standard MR-based attenuation correction (MR-AC). We report on the quantitative effect of not accounting for the attenuation of patient positioning aids in combined PET/MR imaging. METHODS: We used phantom and patient data acquired with positioning aids on a PET/CT scanner (Biograph 16, HI-REZ) to mimic PET/MR imaging conditions. Reference CT-based attenuation maps were generated from measured (original) CT transmission images (origCT-AC). We also created MR-like attenuation maps by following the same conversion procedure of the attenuation values except for the prior delineation and subtraction of the positioning aids from the CT images (modCT-AC). First, a uniform (68)Ge cylinder was positioned centrally in the PET/CT scanner and fixed with a vacuum mattress (10 cm thick) and, in a repeat examination, with MR positioning foam pads. Second, 16 patient datasets were selected for subsequent processing. All patients were regionally immobilized with positioning aids: a vacuum mattress for head/neck imaging (nine patients) and a foam mattress for imaging of the lower extremities (seven patients). PET images were reconstructed following CT-based attenuation and scatter correction using the original and modified (MR-like) CT images: PET(origCT-AC) and PET(modCT-AC), respectively. PET images following origCT-AC and modCT-AC were compared visually and in terms of mean differences of voxels with a standardized uptake value of at least 1.0. In addition, we report maximum activity concentration in lesions for selected patients. RESULTS: In the phantom study employing the vacuum mattress the average voxel activity in PET(modCT-AC) was underestimated by 6.4% compared to PET(origCT-AC), with 3.4% of the PET voxels being underestimated by 10% or more. When the MR foam pads were not accounted for during AC, PET(modCT-AC) was underestimated by 1.1% on average, with none of the PET voxels being underestimated by 10% or more. Evaluation of the head/neck patient data showed a decrease of 8.4% ([(68)Ga]DOTATOC) and 7.4% ([(18)F]FDG) when patient positioning aids were not accounted for during AC, while the corresponding decrease was insignificant for the lower extremities. CONCLUSION: Depending on the size and density of the positioning aids used, a regionally variable underestimation of PET activity following AC is observed when positioning aids are not accounted for. This underestimation may become relevant in combined PET/MR imaging of patients with neuropsychiatric indications, but appears to be of no clinical relevance in imaging the extremities.

Single and dual energy attenuation correction in PET/CT in the presence of iodine based contrast agents.

In present positron emission tomography (PET)/computed tomography (CT) scanners, PET attenuation correction is performed by relying on the information given by a single CT scan. The scaling of the linear attenuation coefficients from CT x-ray energy to PET 511 keV gamma energy is prone to errors especially in the presence of CT contrast agents. Attenuation correction based upon two CT scans at different energies but performed at the same time and patient position should reduce such errors and therefore improve the accuracy of the reconstructed PET images at the cost of introduced additional noise. Such CT scans could be provided by future PET/CT scanners that have either dual source CT or energy sensitive CT. Three different dual energy scaling methods for attenuation correction are introduced and assessed by measurements with a modified NEMA 1994 phantom with different CT contrast agent concentrations. The scaling is achieved by differentiating between (1) Compton and photoelectric effect, (2) atomic number and density, or (3) water-bone and water-iodine scaling schemes. The scaling method (3) is called hybrid dual energy computed tomography attenuation correction (hybrid DECTAC). All three dual energy scaling methods lead to a reduction of contrast agent artifacts with respect to single energy scaling. The hybrid DECTAC method resulted in PET images with the weakest artifacts. Both, the hybrid DECTAC and Compton/photoelectric effect scaling resulted also in images with the lowest PET background variability. Atomic number/density scaling and Compton/photoelectric effect scaling had problems to correctly scale water, hybrid DECTAC scaling and single energy scaling to correctly scale Teflon. Atomic number/density scaling and hybrid DECTAC could be generalized to reduce these problems.

Iodine-124 PET dosimetry in differentiated thyroid cancer: recovery coefficient in 2D and 3D modes for PET(/CT) systems.

PURPOSE: This study evaluated the absolute quantification of iodine-124 ((124)I) activity concentration with respect to the use of this isotope for dosimetry before therapies with (131)I or (131)I-labeled radiotherapeuticals. The recovery coefficients of positron emission tomography(/computed tomography) PET(/CT) systems using (124)I were determined using phantoms and then validated under typical conditions observed in differentiated thyroid cancer (DTC) patients. METHODS: Transversal spatial resolution and recovery measurements with (124)I and with fluorine-18 ((18)F) as the reference were performed using isotope-containing line sources embedded in water and six isotope-containing spheres 9.7 to 37.0 mm in diameter placed in water-containing body and cylinder phantoms. The cylinder phantom spheres were filled with (18)F only. Measurements in two-dimensional (2D) and three-dimensional (3D) modes were performed using both stand-alone PET (EXACT HR(+)) and combined PET/CT (BIOGRAPH EMOTION DUO) systems. Recovery comparison measurements were additionally performed on a GE ADVANCE PET system using the cylinder phantom. The recovery coefficients were directly determined using the activity concentration of circular regions of interest divided by the prepared activity concentration determined by the dose calibrator. The recovery correction method was validated using three consecutive scans of the body phantom under our (124)I PET(/CT) protocol for DTC patients. RESULTS: Compared with that of (18)F, transversal spatial resolution of (124)I was slightly, but statistically significantly degraded (7.4 mm vs. 8.3 mm, P<0.002). Using the body phantom, recovery was lower for (124)I than for (18)F in both 2D and 3D modes. The (124)I recovery coefficient of the largest sphere was significantly higher in 2D than in 3D mode (81% vs. 75%, P=0.03). Remarkably, the (18)F recovery coefficient for the largest sphere significantly deviated from unity (range of 87%-93%, P<0.004) for all scanners but the GE ADVANCE. The maximum range of inaccuracy of the measured (124)I activity concentration under in vivo conditions after applying partial volume correction was +/-10% for spheres > or =12.6 mm in diameter. CONCLUSIONS: Recovery correction is mandatory for (124)I PET quantification, even for large structures. To ensure accurate dosimetry, thorough absolute recovery measurements must be individually established for the particular PET scanner and radionuclide to be used.